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Propofol and Dexmedetomidin vs Midazolam Intraoperative Sedation and POCD

Not Applicable
Recruiting
Conditions
Pertrochanteric Fracture
Postoperative Cognitive Dysfunction
Postoperative Pain, Acute
Interventions
Behavioral: Mini mental state exame (MMSE)
Behavioral: Digit Symbol Substitution Test (DSST)
Diagnostic Test: Numeric rating Scale (NRS)
Diagnostic Test: Postoperative inflammation
Registration Number
NCT05398757
Lead Sponsor
Osijek University Hospital
Brief Summary

This study will examine the effect of intraoperative sedation with midazolam, propofol and dexemdetomidine on the occurrence of postoperative cognitive impairment in patients undergoing surgical treatment of pertrochanteric fracture of the femur.

Detailed Description

Patients undergoing surgical treatment of pertrochanteric femoral fracture by intramedullary fixation will be included in the study. Patients will be older than 65 years and will belong to class I to III anesthesia risk according to the ASA classification. All patients included in the study will sign informed consent. Patients with dementia, mental illness, psychoorganically altered patients, and patients with a contraindication to dexmedetomidine, propofol, midazolam or with a contraindication to spinal anesthesia will be excluded from the study. All patients included in the study will have their blood taken for laboratory analysis of red blood cells, leukocytes, CRP, PCT, ChE and IL-6. Analyzes will be performed before the procedure, on the 1st, 3rd and 5th postoperative day. All patients will be tested for Mini mental state exame (MMSE) score before surgery to rule out pre-existing cognitive impairment, and those patients who have an MMSE value \<17 prior to surgery will be excluded from the study. In premedication, patients will be randomized using three envelopes selected by the blind researcher for the contents of each envelope. According to envelope patients will be divided into three groups: dexmedetomidine group (DS), propofol group (PS) and midazolam group (MS). Neuroaxial spinal block with intrathecal administration of 12.5 - 15 mg 0.5% levobupivacaine in the intervertebral space L3 / L4 or L4 / L5 will be the technique of anesthesia. After spinal block, patients in the DS group will receive a continuous infusion of dexmedetomidine at a dose of 0.5 mcg / kg / h, patients in the PS group will receive a continuous infusion of propofol at a dose of 25-75 mcg / kg / min, while patients in the MS group will receive 0.05-0.07 mg / kg bolus i.v. midazolam. The total dose administered and the duration of surgery will be recorded. The volume of intraoperatively administered crystalloids or blood products will be recorded in all patients included in the study. In the postoperative period, pain will be measured with a numerical rating scale (NRS) 4, 8, 12 and 24 hours after surgery. All patients will receive the usual postoperative analgesia with metamizole and tramadol according to the protocol of the Department. On the 1st, 3rd and 5th postoperative days in the morning between 8.00 and 10.00, all patients will be tested for MMSE and Digit Symbol Substitution Test (DSST) score. A researcher who will evaluate MMSE and DSST values in the postoperative period will be blind to the drug that patients received intraoperatively.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
80
Inclusion Criteria
  • Pertrochanteric fracture surgery
  • Informed consent signed
Exclusion Criteria
  • MMSE before surgery < 17
  • Allergy on midazolam, propofol or dexemdetomidine
  • Contraindication for neuroaxial anesthesia

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
MidazolamMini mental state exame (MMSE)For sedation during surgery, patients will receive i.v. midazolam in dose 0.05 - 0.07 mg/kg.
MidazolamDigit Symbol Substitution Test (DSST)For sedation during surgery, patients will receive i.v. midazolam in dose 0.05 - 0.07 mg/kg.
MidazolamNumeric rating Scale (NRS)For sedation during surgery, patients will receive i.v. midazolam in dose 0.05 - 0.07 mg/kg.
MidazolamPostoperative inflammationFor sedation during surgery, patients will receive i.v. midazolam in dose 0.05 - 0.07 mg/kg.
PropofolMini mental state exame (MMSE)For sedation during surgery, patients will receive i.v. propofol in dose 25-27 mcg/kg/min.
PropofolDigit Symbol Substitution Test (DSST)For sedation during surgery, patients will receive i.v. propofol in dose 25-27 mcg/kg/min.
PropofolNumeric rating Scale (NRS)For sedation during surgery, patients will receive i.v. propofol in dose 25-27 mcg/kg/min.
PropofolPostoperative inflammationFor sedation during surgery, patients will receive i.v. propofol in dose 25-27 mcg/kg/min.
DexmedetomidinMini mental state exame (MMSE)For sedation during surgery, patients will receive i.v. dexmedetomidin in dose 0.5 mcg/kg/h
DexmedetomidinDigit Symbol Substitution Test (DSST)For sedation during surgery, patients will receive i.v. dexmedetomidin in dose 0.5 mcg/kg/h
DexmedetomidinNumeric rating Scale (NRS)For sedation during surgery, patients will receive i.v. dexmedetomidin in dose 0.5 mcg/kg/h
DexmedetomidinPostoperative inflammationFor sedation during surgery, patients will receive i.v. dexmedetomidin in dose 0.5 mcg/kg/h
MidazolamMidazolamFor sedation during surgery, patients will receive i.v. midazolam in dose 0.05 - 0.07 mg/kg.
PropofolPropofolFor sedation during surgery, patients will receive i.v. propofol in dose 25-27 mcg/kg/min.
DexmedetomidinDexmedetomidinFor sedation during surgery, patients will receive i.v. dexmedetomidin in dose 0.5 mcg/kg/h
Primary Outcome Measures
NameTimeMethod
Postoperative inflammation measured by serum IL-6 levels5 days

Postoperative inflammation with respect to intraoperative sedation will be assessed by serum levels IL-6 at postoperative day 1, 3 and 5. Continuous increase of IL-6 in postoperative serial measurements will be considered as systemic inflammation state.

Postoperative inflammation measured by serum PCT levels5 days

Postoperative inflammation with respect to intraoperative sedation will be assessed by serum levels of PCT at postoperative day 1, 3 and 5. PCT \> 0.5 ng/ml and continuous increase in postoperative serial measurements will be considered as systemic inflammation state.

Occurrence of postoperative cognitive dysfunction (POCD) measured by MMSE5 days

The incidence of POCD with respect to intraoperative sedation in the postoperative period will be measured by MMSE test on the first, third and fifth postoperative day. An absolute z-score greater than 1.96 in postoperative testing or a decrease in the postoperative MMSE value by more than 20% relative to the preoperative value will be considered the occurrence of POCD in the postoperative period.

Occurrence of postoperative cognitive dysfunction (POCD) measured by DSST5 days

The incidence of POCD with respect to intraoperative sedation in the postoperative period will be measured by DSST on the first, third and fifth postoperative day. An absolute z-score greater than 1.96 in postoperative testing or a decrease in the postoperative DSST value by more than 20% relative to the preoperative value will be considered the occurrence of POCD in the postoperative period.

Postoperative inflammation measured by serum CRP levels5 days

Postoperative inflammation with respect to intraoperative sedation will be assessed by serum levels of CRP at postoperative day 1, 3 and 5. CRP \> 50 mg/L and rising dynamic of CRP in postoperative serial measurements will be considered as systemic inflammation state.

Postoperative inflammation measured by white blood cells count5 days

Postoperative inflammation with respect to intraoperative sedation will be assessed by serum levels of white blood cells. Leukocytes \> 12.000/mm3 or \< 4.000/mm3 in postoperative serial measurements will be considered as systemic inflammation state.

Postoperative inflammation measured by serum cholinesterase activity5 days

Postoperative inflammation with respect to intraoperative sedation will be assessed by serum cholinesterase activity at postoperative day 1, 3 and 5. Cholinesterase activity \< 4000 U/L in postoperative serial measurements will be considered as systemic inflammation state.

Secondary Outcome Measures
NameTimeMethod
Postoperative pain24 hours

Postoperative pain with respect to intraoperative sedation will be examined by Numeric rating scale (NRS) 4, 8, 12 and 24 hours after surgery. NRS is a scale from 0 to 10, where 0 means no pain and 10 means the strongest pain. NRS above or equal to 4 will be considered inadequate postoperative analgesia.

Trial Locations

Locations (1)

University Hospital Osijek

🇭🇷

Osijek, Croatia

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